RMD Open最新文献

Objective: We aimed to assess the prevalence of clonal haematopoiesis (CH) in patients with giant cell arteritis (GCA) compared with controls and individuals with other autoimmune diseases (AIDs) and to identify high-risk clinical/genetic profiles that could influence disease outcomes.

Methods: In a prospective observational study at three hospitals, we included 49 patients diagnosed with GCA, 48 patients with other AIDs and 27 control participants. We used next-generation sequencing to detect clonal haematopoiesis (CH) among them.

Results: CH was detected in 55.1% of patients with GCA, 59.3% of controls and 18.8% of patients with other AIDs. The most commonly mutated genes in GCA and control groups were DNMT3A and TET2. No significant differences in CH prevalence were found between patients with GCA and controls or other AID when adjusted for age and sex. Cluster analysis revealed two distinct groups within the patients with GCA, one of which displayed a higher prevalence of TET2 and JAK2 variants, and was associated with worse prognosis.

Conclusions: CH is prevalent among patients with GCA but does not differ significantly from controls or other autoimmune conditions. However, specific genetic profiles, particularly mutations in TET2 and JAK2, are associated with a higher risk cluster within the GCA cohort. This observation highlights the interest of detecting CH in patients with GCA in both routine practice and clinical trials for better risk stratification. Further prospective studies are needed to determine if management tailored to the genetic profile would improve outcomes.

Secondary lymphoid organs such as lymph nodes (LNs) are the home of peripheral tolerance mechanisms which control autoreactive T cells and prevent immune responses to self-antigen. In systemic autoimmunity, there is a clear failure of these peripheral tolerance mechanisms that leads to chronic inflammation and tissue destruction, highlighting the role for LNs as possible gatekeepers of autoimmunity. In recent years there has been a shift in research focus towards tissue sites in autoimmune diseases ranging from type 1 diabetes to rheumatoid arthritis in an effort to better characterise pathogenesis and guide diagnostic and therapeutic decisions. Although this has yielded great insight, it fails to tackle the initial break in tolerance that initiates disease progression which is most likely originating in peripheral LNs. In the majority of autoimmune diseases a preclinical phase is recognised. This is characterised by the presence of autoantibodies, which is indicative of a break in immune tolerance, and the absence of clinically apparent inflammation or tissue destruction. This review explores how our current knowledge of LNs in the preclinical and established phases of autoimmune diseases provides insight into possibly shared pathological mechanisms that drive disease progression and highlight the gaps in our knowledge that may help uncover new therapeutic avenues for intervention and prevention.

Objectives: To compare the construct validity, including discrimination between known groups, of three pain and three morning stiffness (MS) measurement instruments.

Methods: Patients with radiographic axial spondyloarthritis with 8-year data from the Outcome in Ankylosing Spondylitis International Study cohort were assessed cross-sectionally. Three instruments for pain and three for MS, all self-reported and scored 0-10, were compared. Construct validity was evaluated by testing (1) hypothesis of correlations' strength and (2) discrimination between known groups using standardised mean differences (SMD) across external constructs. Influence of contextual factors (CFs) on SMDs was investigated.

Results: Of 85 patients, mean age was 54 (SD 11), mean symptom duration 31 (11) years, 71% males. All six instruments showed a good construct validity by fulfilling >75% of the hypotheses for the strength of correlation. Neck/back/hip pain (Bath Ankylosing Spondylitis Disease Activity Index-Question 2, BASDAI-Q2) and total back pain had higher SMDs compared with back pain at night across all between-group comparisons, with BASDAI-Q2 performing mostly slightly better (eg, SMD for external construct Axial Spondyloarthritis Disease Activity Score (ASDAS; ≥2.1 vs <2.1): 1.87 (BASDAI-Q2) vs 1.56 (total back pain) vs 1.07 (back pain at night)). MS-severity and severity/duration had higher SMDs across all external constructs (with MS-severity slightly better), while MS-duration performed worse (eg, SMD external construct ASDAS: 1.51 (MS-severity) and 1.39 (MS-severity/duration) vs 1.16 (MS-duration)). Influence of CFs on known group discrimination was limited.

Conclusions: The recommended Assessment of SpondyloArthritis international Society Core Outcome Set (ASAS-COS) pain measurement instrument total back pain BASDAI-Q2 has the best known group discrimination. For MS, the ASAS-COS stiffness measure (MS-severity/duration) performs well although MS-severity even slightly better. Known group discrimination is overall stable across CFs.

Background and aims: Systemic sclerosis (SSc) is an autoimmune connective disease characterised by excessive extracellular matrix deposition and widespread skin and internal organ fibrosis including various cardiac manifestations. Heart involvement is one of the leading causes of death among patients with SSc. In this study, we aimed to assess the effect of various vasodilator treatments.

Methods: We used data from a national multicentric prospective study using the French SSc national database. We estimated the average treatment effect (ATE) of sildenafil, bosentan, angiotensin-converting enzyme (ACE) inhibitors and iloprost on diastolic dysfunction, altered ejection fraction <50% and pulmonary arterial hypertension (PAH) using a causal method, namely the longitudinal targeted minimum loss-based estimation, to adjust for confounding and informative censoring.

Results: We included 1048 patients with available data regarding treatment. Regarding sildenafil analyses, the ATE on diastolic dysfunction at 3 years was -2.83% (95% CI -4.06; -1.60, p<0.00001), and the estimated ATE on altered ejection fraction <50% was -0.88% (95% CI -1.70; -0.05, p=0.037). We did not find a significative effect on PAH. Regarding bosentan, ACE inhibitors and iloprost, none of them neither showed a significant effect on diastolic dysfunction, altered ejection fraction <50% or PAH.

Conclusions: Using causal methods, our study is the first and largest suggesting that sildenafil might have benefits among SSc patients regarding diastolic dysfunction and altered ejection fraction occurrence. However, further studies assessing the effect of vasodilators on heart-related outcome among SSc patients are needed to confirm those exploratory results.

Purpose: To assess sickness absence and transitions from employment for employees with arthritis compared with employees without arthritis over time.

Methods: We use 10 waves of the UK Household Longitudinal Survey (2009-2019). The sample (n=38 928) comprises employees aged 50 years to state retirement age. Arthritis was self-reported and could refer to people with conditions under the umbrella term 'inflammatory arthritis' or osteoarthritis (hereafter 'arthritis'). Weighted random-effects multivariable linear probability models were estimated for two employment-related measures (1) sickness absence and (2) transitions from employment to: (a) unemployment; (b) long-term sick; (c) early retirement. These were regressed against a variable for arthritis and confounding factors (age, socioeconomic job classification, employing sector, year and additional health conditions). Additional analyses examined an interaction between the variable arthritis and these factors to test whether the effect of arthritis differs between these groups.

Results: Employees reporting having arthritis were more likely to have sickness absence (1.35 percentage points greater rate (95% CI (0.92, 1.78)) and to transition to long-term sick (0.79 percentage points (0.46, 1.13)) and early retirement (0.58 percentage points (0.05, 1.11)). No effect was found for transitions to unemployment. There was limited evidence that the effects of arthritis vary for employees in different socioeconomic classifications.

Conclusions: Employees living with arthritis have higher rates of sickness absence and greater rates of transitions from employment to long-term sick and early retirement. Further work could look at ways to quantify the implications for individuals, employers and the state and ways to alleviate the effects of living with arthritis on work participation.

Background: The impact of disease activity and treatment on fertility outcomes in patients with spondyloarthritis (SpA) has been little explored. This study aimed to describe median time to pregnancy (TTP) in women with SpA and the factors influencing TTP in this population.

Methods: This prospective observational multicentre (63 centres) French cohort (GR2 study-NCT02450396) included consecutive women with a diagnosis of SpA (according to their rheumatologist) who wanted to become pregnant between 2015 and 2021. TTP (in months) was the main outcome criterion, prospectively calculated from the date of study inclusion to the date of conception. Data on demographics, disease characteristics, disease activity, severity and treatment were prospectively collected at inclusion and each year thereafter until pregnancy occurred. TTP and its associated factors were estimated by survival analysis (Shared Frailty Cox models), with a random centre effect and multiple imputation to address missing data.

Results: We analysed 88 women included before conception. Among them, 56 (63.6%) became pregnant during follow-up. Median TTP was 16.1 (95% CI (12.2 to 25.3)) months. Mean preconceptional Bath Ankylosing Spondylitis Disease Activity Index at inclusion was 2.9 (±SD 2.1). Patients were treated with TNF inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs and glucocorticoids in 61 (69.3%), 23 (26.1%), 12 (13.6%) and 8 (9.1%) cases, respectively. The multivariate model found a significant association between TTP and age (HR) (per year) 1.22 95% CI (1.08 to 1.40); p<0.001) and the use of NSAIDs during preconception (HR 3.01 95% CI (2.15 to 3.85); p=0.01).

Conclusion: Age and NSAID use during preconception were significantly associated with a longer TTP, after adjustment for other confounding factors. These findings warrant caution in the use of NSAIDs in SpA patients trying to conceive.

Objectives: To explore the association between the extent of CT abnormalities by quantitative imaging analysis (QIA) and clinical/physiological disease parameters in patients with antisynthetase syndrome associated interstitial lung disease (ARS-ILD).

Methods: We analysed 20 patients with antisynthetase antibodies and active ILD enrolled in the Abatacept in Myositis-Associated Interstitial Lung Disease study. High-resolution chest CT was obtained at weeks 0, 24 and 48 and QIA scored the extent of ground glass (quantitative score for ground glass), fibrosis (quantitative score for lung fibrosis, QLF) and total ILD (quantitative ILD, QILD). Mixed-effects models estimated longitudinal QIA scores over time. Associations between QIA scores with clinical/physiological parameters were analysed longitudinally using repeated-measures mixed-effects models.

Results: Patients were median age 57 years, 55% males and 85% white. Higher (worse) baseline QIA scores correlated with lower baseline forced vital capacity (FVC) and diffusing capacity adjusted for haemoglobin (DLCO). Longitudinal QIA trajectories trended towards improving scores during the trial, and patients on O₂ at baseline had worsening QIA trajectories which were different from patients who were not on O₂. Longitudinal QIA scores demonstrated strong associations with both FVC and DLCO over time. Higher QILD scores over time were also associated with worse dyspnoea scores, pulmonary visual analogue scale, physician and patient global disease activity, health status in 6/8 domains of the Short Form-36 and higher oxygen requirements. Patients with significant radiographic improvement at 48 weeks had higher baseline QLF, QILD and worse DLCO.

Conclusions: Longitudinal QIA scores associate with lung physiology, patient perception of respiratory status, overall disease activity and quality of life over time in ARS-ILD. QIA may allow reproducible monitoring of disease progression and response to therapy over time.

Trial registration number: NCT03215927.

Objectives: In axial spondyloarthritis (axSpA), early diagnosis is crucial, but diagnostic delay remains long and diagnostic criteria do not exist. We aimed to identify a diagnostic model that distinguishes patients with axSpA from patients without axSpA with chronic back pain based on clinical data in routine care.

Methods: Clinical data from patients with chronic back pain were used, with information on rheumatological examinations based on clinical indications. The total dataset was randomly divided into training and test datasets at a 7:3 ratio. A machine learning-based model was built to distinguish axSpA from non-axSpA using the random forest algorithm. Overall accuracy, sensitivity, specificity and the area under the receiver operating characteristic curve-area under the curve (ROC-AUC) in the test dataset were calculated. The contribution of each variable to the accuracy of the model was assessed.

Results: Data from 939 randomly selected patients were available: 659 diagnosed with axSpA and 280 with non-axSpA. In the test dataset, the model reached an accuracy of 0.9234, a sensitivity of 0.9586, a specificity of 0.8438 and a ROC-AUC of 0.9717. Human leucocyte antigen B27 (HLA-B27) contributed most to the accuracy of the model; that is, the accuracy would suffer most from not using HLA-B27, followed by insidious onset of back pain and erosions in the sacroiliac joint.

Conclusions: We provide a machine learning-based model that reveals high performance in diagnosing patients with chronic back pain with axSpA versus without axSpA based on information from a tertiary rheumatology practice. This model has the potential to improve diagnostic delay in patients with axSpA in daily routine settings.

Objective: Systemic sclerosis Impact of Disease (ScleroID) is the first comprehensive patient-reported outcome measure (PROM) specifically developed for systemic sclerosis (SSc). We investigated the performance of ScleroID in patients with diffuse cutaneous SSc (dcSSc), as a prerequisite for its use in randomised controlled trials (RCTs) testing potentially disease-modifying drugs.

Methods: All patients with dcSSc from the large, multicentric, ScleroID cohort were included. SSc-Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions and 36-item Short Form Health Survey (SF-36) were used as comparators. The study includes a longitudinal arm with a reliability visit at 7±3 days and a 12 months follow-up visit. The performance of ScleroID in dcSSc was assessed according to the Outcome Measures in Rheumatology filter.

Results: In total, 152 dcSSc patients were analysed (29% male, median age 54 years). ScleroID reflected well the disease impact of dcSSc, showing a good construct validity with high Spearman's correlation coefficients with comparators (SSc-HAQ, 0.79, 95% CI (0.69, 0.86); HAQ-Disability Index, 0.72 95% CI (0.60, 0.80); SF-36 physical score, -0.69 95% CI (-0.77, -0.60)). The internal consistency was strong (Cronbach's alpha 0.87, split-half reliability coefficient 0.88).In the longitudinal arm, 44 patients had a reliability visit and 113 had a follow-up visit, of whom 19/113 (17%) reported a significant change (11 improved, 8 worsened). ScleroID showed a good consistency and discriminative ability with excellent test-retest reliability (intraclass correlation coefficient 0.89, 95% CI (0.84, 0.92)) and moderate sensitivity to change (standardised response mean -0.63 in the improved subgroup and 0.48 in the worsened subgroup), but superior to the comparators.

Conclusion: The European Alliance of Associations for Rheumatology (EULAR) ScleroID performs well for patients with dcSSc. This supports its inclusion and regular assessment as PROM in RCTs.